Osteoporosis contributes to decreased bone mass and bone mineral density (BMD) as well as compromised fracture healing rates and bone repair quality. Tissue engineering offers novel strategies to repair large bone defects, but it remains a big challenge in orthopaedic surgery to repair large bone defects, especially in osteoporotic patients. Recently, adipose-derived stem cells (ASCs) were reported to be able to differentiate into the osteogenic lineage. Moreover, ASCs can maintain stable stem cell properties during the aging process, indicating their potential application in bone regeneration in osteoporotic patients.
The aim of this study is to evaluate proliferation and osteogenic potential of osteoporotic ASCs in vitro, and the bone regeneration capability of autologous osteo-induced ASCs in poly(lactic-co-glycolic acid) (PLGA) constructs implanted in osteoporotic rat calvarial defects. A total of eighty 6-month-old female Sprague-Dawley rats will be randomly assigned into either the ovariectomy group (n=40) or the sham operation group (n=40). Four months after the operation, the BMD of the entire femur of ten rats in each group will be measured. The rat ASCs from both groups will be cultured in monolayer or three-dimension (3D, seeding ASCs into PLGA mesh) with osteogenic medium (osteo-induced) or growth medium (non-induced) for three weeks. ASC proliferation and osteogenic differentiation will be evaluated using immunofluorescence staining, quantitative ELISA, biochemical assays, and real-time PCR. The remaining thirty rats in each group will have 5-mm-diameter-calvarial-defects created bilaterally. One defect will be randomly implanted with autologous osteo-induced ASC- or non-induced ASC-based premature constructs (n = 15 in each group). PLGA mesh alone implanted in another defect will serve as a control. Six weeks, 12 weeks, and one year post implantation, five rats in each subgroup will be sacrificed and the defect healing will be evaluated using radiodensitometric analysis, BMD measurement, 5CT, H&E and Masson staining, and biomechanical testing. Tracking of ASCs by quantum dots (QDs) labeling will also be performed to confirm the direct role of ASCs during bone regeneration. This study may broaden ASCs'application range in bone tissue engineering and give a bench-to-bedside option for large bone defect repair in osteoporotic patients.

Public Health Relevance

Large bone defects in osteoporotic patients are a big challenge for clinical treatment, in which autologous adipose-derived stem cells (ASCs)-based tissue engineering may be a promising approach due to ASCs unique genetic property.
The aim of this study is to evaluate proliferation and osteogenic potential of osteoporotic ASCs in vitro, and the bone regeneration capability of autologous osteo-induced ASCs in poly(lactic-co-glycolic acid) (PLGA) constructs implanted in osteoporotic rat calvarial defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE021433-02
Application #
8227986
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Lumelsky, Nadya L
Project Start
2011-03-01
Project End
2013-12-28
Budget Start
2012-03-01
Budget End
2013-12-28
Support Year
2
Fiscal Year
2012
Total Cost
$111,000
Indirect Cost
$36,000
Name
West Virginia University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Pei, Ming; Li, Jingting; McConda, David B et al. (2015) A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats. Bone 78:1-10
Zhang, Ying; Pizzute, Tyler; Pei, Ming (2014) Anti-inflammatory strategies in cartilage repair. Tissue Eng Part B Rev 20:655-68
Li, Jingting; Ohliger, James; Pei, Ming (2014) Significance of epigenetic landscape in cartilage regeneration from the cartilage development and pathology perspective. Stem Cells Dev 23:1178-94
Li, Jingting; Hansen, Kirk C; Zhang, Ying et al. (2014) Rejuvenation of chondrogenic potential in a young stem cell microenvironment. Biomaterials 35:642-53
Li, Jingting; Campbell, Douglas D; Bal, George K et al. (2014) Can arthroscopically harvested synovial stem cells be preferentially sorted using stage-specific embryonic antigen 4 antibody for cartilage, bone, and adipose regeneration? Arthroscopy 30:352-61
Pei, Ming; Li, Jingting; Zhang, Ying et al. (2014) Expansion on a matrix deposited by nonchondrogenic urine stem cells strengthens the chondrogenic capacity of repeated-passage bone marrow stromal cells. Cell Tissue Res 356:391-403
Pei, Ming; Zhang, Ying; Li, Jingting et al. (2013) Antioxidation of decellularized stem cell matrix promotes human synovium-derived stem cell-based chondrogenesis. Stem Cells Dev 22:889-900
Shoukry, Mark; Li, Jingting; Pei, Ming (2013) Reconstruction of an in vitro niche for the transition from intervertebral disc development to nucleus pulposus regeneration. Stem Cells Dev 22:1162-76